knitr::opts_chunk$set(echo = T, root.dir="~/Desktop/APOE_finemapping")
knitr::opts_knit$set(root.dir="~/Desktop/APOE_finemapping")

library(dplyr)
library(ggplot2)

library(echolocatoR)

Import fine-mapping results

Query fine-mapping portal

Download Alzheimer’s Disease GWAS fine-mapping results for the APOE locus via the echolocatoR Fine-mapping Portal API.

local_finemap <- echolocatoR::GITHUB.portal_query(dataset_types = "GWAS", 
                                                 phenotypes = "Alzheimer", 
                                                 LD_panels = c("UKB", "1KGphase3"),
                                                 loci = "APOE", 
                                                 file_types = "multi_finemap", 
                                                 results_dir = "./data", 
                                                 overwrite = F)
## [1] "Fetching echolocatoR Fine-mapping Portal study metadata."
## [1] "+ 4 datasets remain after filtering."
## [1] "+ Searching for multi_finemap files..."
## [1] "+ 2 unique files identified."
## [1] "+ Downloading 2 files..."
## [1] "+ Returning local file paths."

Merge fine-mapping results

finemap_dat <- lapply(local_finemap,function(x){
  dataset <- basename(dirname(dirname(dirname(x))))
  LD_ref <- stringr::str_split(basename(x),pattern = "[.]")[[1]][2]
  printer("Importing",dataset)
  dat <- data.table::fread(x) 
  cbind(dataset=dataset, 
        LD_ref=LD_ref, 
        dat)
}) %>% data.table::rbindlist()
## [1] "Importing Jansen_2018"
## [1] "Importing Marioni_2018"

Identify credible sets

Show just the Union Credible Set SNPs (SNPs nominated by at least 1/4 fine-mapping tools).

ucs_snps <- subset(finemap_dat, Support>0)
createDT(ucs_snps)

Identify Consensus SNPs

Filter to just the consensus SNPs (SNPs nominated by 2 or more fine-mapping tools).

consensus_snps <- subset(finemap_dat, Consensus_SNP==T)
createDT(consensus_snps)

Cell-type-specific annotations

Epigenomic peak overlap

finemap_dat$Gene<- finemap_dat$Locus
finemap_dat$Locus <- paste(finemap_dat$Locus,finemap_dat$dataset,sep="_")
plot_res <- echolocatoR::SUMMARISE.peak_overlap_plot(merged_DT = finemap_dat,
                                                     snp_filter = "Support>0",
                                                     include.NOTT_2019_peaks = T,
                                        include.NOTT_2019_enhancers_promoters = T,
                                        include.NOTT_2019_PLACseq = T,
                                        include.CORCES_2020_scATACpeaks = T,
                                        include.CORCES_2020_Cicero_coaccess = T,
                                        include.CORCES_2020_bulkATACpeaks = T,
                                        include.CORCES_2020_HiChIP_FitHiChIP_coaccess = T,
                                      include.CORCES_2020_gene_annotations = T,
                                      plot_celltype_specificity = T,
                                      plot_celltype_specificity_genes = T)
## [1] "++ NOTT_2019:: Downloading and merging 12 peaks BED files."
## [1] "++ NOTT_2019:: Converting merged BED files to GRanges."
## [1] "++ NOTT_2019:: 634540 ranges retrieved."
## [1] "Importing Astrocyte enhancers ..."
## [1] "Importing Astrocyte promoters ..."
## [1] "Importing Neuronal enhancers ..."
## [1] "Importing Neuronal promoters ..."
## [1] "Importing Oligo enhancers ..."
## [1] "Importing Oligo promoters ..."
## [1] "Importing Microglia enhancers ..."
## [1] "Importing Microglia promoters ..."
## [1] "++ Converting to GRanges."
## [1] "Importing Microglia interactome ..."
## [1] "Importing Neuronal interactome ..."
## [1] "Importing Oligo interactome ..."
## [1] "CORCES_2020:: Extracting overlapping cell-type-specific scATAC-seq peaks"
## Error in `[[<-`(`*tmp*`, name, value = "scATAC") : 
##   1 elements in value to replace 0 elements
## [1] "CORCES_2020:: Extracting overlapping bulkATAC-seq peaks from brain tissue"
## Error in `[[<-`(`*tmp*`, name, value = "bulkATAC") : 
##   1 elements in value to replace 0 elements

Show the epigenomic overlap results

createDT(plot_res$data)

Summarise assay counts

Summarise the number of assays in which at least one UCS SNP overlapped with a cell-type-specific epigenomic peak.

celltype_counts <- plot_res$data %>% 
  dplyr::group_by(Locus, Cell_type) %>%
  dplyr::summarise(Count=sum(Count,na.rm = T)) %>%
  dplyr::arrange(Locus, desc(Count))
## `summarise()` has grouped output by 'Locus'. You can override using the `.groups` argument.
createDT(celltype_counts)

Session info

sessioninfo::session_info()
## ─ Session info ───────────────────────────────────────────────────────────────
##  setting  value                       
##  version  R version 4.0.4 (2021-02-15)
##  os       macOS Big Sur 10.16         
##  system   x86_64, darwin17.0          
##  ui       X11                         
##  language (EN)                        
##  collate  en_GB.UTF-8                 
##  ctype    en_GB.UTF-8                 
##  tz       Europe/London               
##  date     2021-03-19                  
## 
## ─ Packages ───────────────────────────────────────────────────────────────────
##  package              * version  date       lib source        
##  AnnotationDbi          1.52.0   2020-10-27 [1] Bioconductor  
##  AnnotationFilter       1.14.0   2020-10-27 [1] Bioconductor  
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##  askpass                1.1      2019-01-13 [1] CRAN (R 4.0.2)
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##  backports              1.2.1    2020-12-09 [1] CRAN (R 4.0.2)
##  base64enc              0.1-3    2015-07-28 [1] CRAN (R 4.0.2)
##  Biobase                2.50.0   2020-10-27 [1] Bioconductor  
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##  BiocGenerics           0.36.0   2020-10-27 [1] Bioconductor  
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##  BiocParallel           1.24.1   2020-11-06 [1] Bioconductor  
##  biomaRt                2.46.3   2021-02-11 [1] Bioconductor  
##  Biostrings             2.58.0   2020-10-27 [1] Bioconductor  
##  biovizBase             1.38.0   2020-10-27 [1] Bioconductor  
##  bit                    4.0.4    2020-08-04 [1] CRAN (R 4.0.2)
##  bit64                  4.0.5    2020-08-30 [1] CRAN (R 4.0.2)
##  bitops                 1.0-6    2013-08-17 [1] CRAN (R 4.0.2)
##  blob                   1.2.1    2020-01-20 [1] CRAN (R 4.0.2)
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##  BSgenome               1.58.0   2020-10-27 [1] Bioconductor  
##  bslib                  0.2.4    2021-01-25 [1] CRAN (R 4.0.2)
##  cachem                 1.0.4    2021-02-13 [1] CRAN (R 4.0.2)
##  checkmate              2.0.0    2020-02-06 [1] CRAN (R 4.0.2)
##  class                  7.3-18   2021-01-24 [1] CRAN (R 4.0.4)
##  cli                    2.3.1    2021-02-23 [1] CRAN (R 4.0.2)
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##  crayon                 1.4.1    2021-02-08 [1] CRAN (R 4.0.2)
##  crosstalk              1.1.1    2021-01-12 [1] CRAN (R 4.0.2)
##  curl                   4.3      2019-12-02 [1] CRAN (R 4.0.1)
##  data.table             1.13.6   2020-12-30 [1] CRAN (R 4.0.4)
##  DBI                    1.1.1    2021-01-15 [1] CRAN (R 4.0.2)
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##  DescTools              0.99.40  2021-02-03 [1] CRAN (R 4.0.2)
##  dichromat              2.0-0    2013-01-24 [1] CRAN (R 4.0.2)
##  digest                 0.6.27   2020-10-24 [1] CRAN (R 4.0.2)
##  dnet                   1.1.7    2020-02-20 [1] CRAN (R 4.0.2)
##  dplyr                * 1.0.5    2021-03-05 [1] CRAN (R 4.0.2)
##  DT                     0.17     2021-01-06 [1] CRAN (R 4.0.2)
##  e1071                  1.7-4    2020-10-14 [1] CRAN (R 4.0.2)
##  echolocatoR          * 0.1.2    2021-03-19 [1] local         
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##  expm                   0.999-6  2021-01-13 [1] CRAN (R 4.0.2)
##  fansi                  0.4.2    2021-01-15 [1] CRAN (R 4.0.2)
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##  GenomicAlignments      1.26.0   2020-10-27 [1] Bioconductor  
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##  GenomicRanges          1.42.0   2020-10-27 [1] Bioconductor  
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##  ggbio                  1.38.0   2020-10-27 [1] Bioconductor  
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##  hms                    1.0.0    2021-01-13 [1] CRAN (R 4.0.2)
##  htmlTable              2.1.0    2020-09-16 [1] CRAN (R 4.0.2)
##  htmltools              0.5.1.1  2021-01-22 [1] CRAN (R 4.0.2)
##  htmlwidgets            1.5.3    2020-12-10 [1] CRAN (R 4.0.2)
##  httr                   1.4.2    2020-07-20 [1] CRAN (R 4.0.2)
##  igraph                 1.2.6    2020-10-06 [1] CRAN (R 4.0.2)
##  IRanges                2.24.1   2020-12-12 [1] Bioconductor  
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##  jquerylib              0.1.3    2020-12-17 [1] CRAN (R 4.0.2)
##  jsonlite               1.7.2    2020-12-09 [1] CRAN (R 4.0.2)
##  knitr                  1.31     2021-01-27 [1] CRAN (R 4.0.2)
##  labeling               0.4.2    2020-10-20 [1] CRAN (R 4.0.2)
##  lattice                0.20-41  2020-04-02 [1] CRAN (R 4.0.4)
##  latticeExtra           0.6-29   2019-12-19 [1] CRAN (R 4.0.2)
##  lazyeval               0.2.2    2019-03-15 [1] CRAN (R 4.0.2)
##  lifecycle              1.0.0    2021-02-15 [1] CRAN (R 4.0.3)
##  lmom                   2.8      2019-03-12 [1] CRAN (R 4.0.2)
##  magrittr               2.0.1    2020-11-17 [1] CRAN (R 4.0.2)
##  MASS                   7.3-53.1 2021-02-12 [1] CRAN (R 4.0.2)
##  Matrix                 1.3-2    2021-01-06 [1] CRAN (R 4.0.4)
##  MatrixGenerics         1.2.1    2021-01-30 [1] Bioconductor  
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##  R6                     2.5.0    2020-10-28 [1] CRAN (R 4.0.2)
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## 
## [1] /Library/Frameworks/R.framework/Versions/4.0/Resources/library